Medical treatment often requires the administration of a therapeutic agent (e.g., medicament, drugs, etc.) to a particular part of a patient's body. As patients live longer and are diagnosed with chronic and/or debilitating ailments, the likely result will be an increased need to place even more protein therapeutics, small-molecule drugs, and other medications into targeted areas throughout the patient's body. Some maladies, however, are difficult to treat with currently available therapies and/or require administration of drugs to anatomical regions to which access is difficult to achieve.
A patient's eye is a prime example of a difficult-to-reach anatomical region, and many vision-threatening diseases, including retinitis pigmentosa, age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, are difficult to treat with many of the currently available therapies. For example, oral medications can have systemic side effects; topical applications may sting and engender poor patient compliance; injections generally require a medical visit, can be painful, and risk infection; and sustained-release implants must typically be removed after their supply is exhausted (and generally offer limited ability to change the dose in response to the clinical picture).
Another example is cancer, such as breast cancer or meningiomas, where large doses of highly toxic chemotherapies, such as rapamycin, bevacizumab (e.g., AVASTIN), or irinotecan (CPT-11), are typically administered to the patient intravenously, which may result in numerous undesired side effects outside the targeted area. Yet another example is drug delivery to the knee, where drugs often have difficulty penetrating the avascular cartilage tissue for diseases such as osteoarthritis.
Implantable drug-delivery devices (e.g., drug-delivery pumps), which may have a refillable drug reservoir, a cannula for delivering the drug, a check valve, etc., generally allow for controlled delivery of pharmaceutical solutions to a specified target. As drug within the drug reservoir depletes, the physician can refill the reservoir with, for example, a syringe, while leaving the device implanted within the patient's body. This approach can minimize the surgical incision needed for implantation and typically avoids future or repeated invasive surgery or procedures.
Implantable drug-delivery pumps, particularly in ocular applications, often utilize a passive mechanism for drug delivery (e.g., pumping the drug out when a finger is pressed on the drug reservoir). One limitation of these conventional, passively-driven drug-delivery pumps is their inability to dynamically respond to changes inside the pump (e.g., failures, blockages, etc.) or to changes in the drug-delivery target area (e.g., increased pressure, bending of the pump's cannula, inflammation causing pressure around the cannula, etc.). The ability to respond to such changes can improve not only the therapeutic value of a pump, but also safety.
Active drug-delivery pumps, particularly feedback-driven ones, represent a substantial improvement over passively-driven pumps. Typically, these feedback-driven pumps are electrically-driven mechanical pumps. They generally employ controller units that receive inputs from sensors that monitor the target treatment area and, in response, direct the release of a pharmaceutical or therapeutic agent to achieve a desired result. The amount of drug released in each dosage period is thus largely determined by the current conditions of the target area and is intended to be variable depending on what the conditions of the target area warrant.
Pharmaceutical treatment regimens may, however, require that a drug be administered in fixed amounts at regular time intervals regardless of the changing conditions in the drug-delivery target area. Since the dosage levels produced by existing closed-loop feedback-driven systems can be highly dependent on the parameters of the treatment area and thus prone to fluctuations, they are inadequate for delivering fixed drug dosages at periodic intervals. For example, changes in the conditions of the target area, such as blockages or other biochemical or physiological events, may lead to variable levels of drug being delivered to the target area. Accordingly, there is a need for a feedback-driven pump that maintains the target dosage level despite such changes.
Furthermore, while feedback based on the conditions of the target area is important in numerous therapeutic applications, errors in drug administration can also arise from changing conditions within the pump itself. Conventional pumps generally do not account for such changes, which can also lead to variable amounts of drug being released. Accordingly, there is also a need for a drug-delivery pump that dynamically responds to changing conditions within the pump itself in order to, for example, consistently release a fixed dosage of drug at periodic time intervals.